tbuckley/cabot-search huggingface dataset:
USE-Evaluator: Performance metrics for medical image segmentation models supervised by uncertain, small or empty reference annotations in neuroimaging
Authors: Sophie Ostmeier, Brian Axelrod, Fabian Isensee, Jeroen Bertels, Michael Mlynash, Soren Christensen, Maarten G. Lansberg, Gregory W. Albers, Rajen Sheth, Benjamin F.J. Verhaaren, Abdelkader Mahammedi, Li-Jia Li, Greg Zaharchuk, Jeremy J. Heit
Journal: Medical Image Analysis (2023)
Glycolytic neutrophils accrued in the spleen compromise anti-tumour T cell immunity in breast cancer
Authors: Yu Wang, Muhan Xu, Jian Sun, Xiaoxiao Li, Huazheng Shi, Xuefeng Wang, Benming Liu, Tao Zhang, Xu Jiang, Liangyu Lin, Qing Li, Yin Huang, Yong Liang, Mingyuan Hu, Fanjun Zheng, Fengyu Zhang, Jian Sun, Yufang Shi, Ying Wang
Journal: Nature Metabolism (2023)
First-line durvalumab and tremelimumab with chemotherapy in RAS-mutated metastatic colorectal cancer: a phase 1b/2 trial
Authors: Marion Thibaudin, Jean-David Fumet, Benoist Chibaudel, Jaafar Bennouna, Christophe Borg, Jerome Martin-Babau, Romain Cohen, Marianne Fonck, Julien Taieb, Emeric Limagne, Julie Blanc, Elise Ballot, Léa Hampe, Marjorie Bon, Susy Daumoine, Morgane Peroz, Hugo Mananet, Valentin Derangère, Romain Boidot, Henri-Alexandre Michaud, Caroline Laheurte, Olivier Adotevi, Aurélie Bertaut, Caroline Truntzer, François Ghiringhelli
Journal: Nature Medicine (2023)

Although patients with microsatellite instable metastatic colorectal cancer (CRC) benefit from immune checkpoint blockade, chemotherapy with targeted therapies remains the only therapeutic option for microsatellite stable (MSS) tumors. The single-arm, phase 1b/2 MEDITREME trial evaluated the safety and efficacy of durvalumab plus tremelimumab combined with mFOLFOX6 chemotherapy in first line, in 57 patients with RAS-mutant unresectable metastatic CRC. Safety was the primary objective of phase Ib; no safety issue was observed. The phase 2 primary objective of efficacy in terms of 3-month progression-free survival (PFS) in patients with MSS tumors was met, with 3-month PFS of 90.7% (95% confidence interval (CI): 79.2-96%). For secondary objectives, response rate was 64.5%; median PFS was 8.2 months (95% CI: 5.9-8.6); and overall survival was not reached in patients with MSS tumors. We observed higher tumor mutational burden and lower genomic instability in responders. Integrated transcriptomic analysis underlined that high immune signature and low epithelial-mesenchymal transition were associated with better outcome. Immunomonitoring showed induction of neoantigen and NY-ESO1 and TERT blood tumor-specific T cell response associated with better PFS. The combination of durvalumab-tremelimumab with mFOLFOX6 was tolerable with promising clinical activity in MSS mCRC. Clinicaltrials.gov identifier: NCT03202758 .
Valvular heart disease and cardiomyopathy: reappraisal of their interplay
Authors: Nina Ajmone Marsan, Francesca Graziani, Maria Chiara Meucci, Hoi W. Wu, Rosa Lillo, Jeroen J. Bax, Francesco Burzotta, Massimo Massetti, J. Wouter Jukema, Filippo Crea
Journal: Nature Reviews Cardiology (2023)
Cortical astrocytes modulate dominance behavior in male mice by regulating synaptic excitatory and inhibitory balance
Authors: Kyungchul Noh, Woo-Hyun Cho, Byung Hun Lee, Dong Wook Kim, Yoo Sung Kim, Keebum Park, Minkyu Hwang, Ellane Barcelon, Yoon Kyung Cho, C. Justin Lee, Bo-Eun Yoon, Se-Young Choi, Hye Yoon Park, Sang Beom Jun, Sung Joong Lee
Journal: Nature Neuroscience (2023)
Genome-wide prediction of disease variant effects with a deep protein language model
Authors: Nadav Brandes, Grant Goldman, Charlotte H. Wang, Chun Jimmie Ye, Vasilis Ntranos
Journal: Nature Genetics (2023)

Predicting the effects of coding variants is a major challenge. While recent deep-learning models have improved variant effect prediction accuracy, they cannot analyze all coding variants due to dependency on close homologs or software limitations. Here we developed a workflow using ESM1b, a 650-million-parameter protein language model, to predict all ~450 million possible missense variant effects in the human genome, and made all predictions available on a web portal. ESM1b outperformed existing methods in classifying ~150,000 ClinVar/HGMD missense variants as pathogenic or benign and predicting measurements across 28 deep mutational scan datasets. We further annotated ~2 million variants as damaging only in specific protein isoforms, demonstrating the importance of considering all isoforms when predicting variant effects. Our approach also generalizes to more complex coding variants such as in-frame indels and stop-gains. Together, these results establish protein language models as an effective, accurate and general approach to predicting variant effects.
Daratumumab monotherapy for refractory lupus nephritis
Authors: Dario Roccatello, Roberta Fenoglio, Ilaria Caniggia, Joelle Kamgaing, Carla Naretto, Irene Cecchi, Elena Rubini, Daniela Rossi, Emanuele De Simone, Giulio Del Vecchio, Martina Cozzi, Savino Sciascia
Journal: Nature Medicine (2023)

Treatment-refractory lupus nephritis (LN) has a high risk of a poor outcome and is often life-threatening. Here we report a case series of six patients (one male and five females) with a median age of 41.3 years (range, 20-61 years) with refractory LN who received renal biopsies and were subsequently treated with intravenous daratumumab, an anti-CD38 monoclonal antibody (weekly for 8 weeks, followed by eight biweekly infusions and up to eight monthly infusions). One patient did not show any improvement after 6 months of therapy, and daratumumab was discontinued. In five patients, the mean disease activity, as assessed by the Systemic Lupus Erythematosus Disease Activity 2000 index, decreased from 10.8 before treatment to 3.6 at 12 months after treatment. Mean proteinuria (5.6 g per 24 h to 0.8 g per 24 h) and mean serum creatinine (2.3 mg dl-1 to 1.5 mg dl-1) also decreased after 12 months. Improvement of clinical symptoms was accompanied by seroconversion of anti-double-stranded DNA antibodies; decreases in median interferon-gamma levels, B cell maturation antigen and soluble CD163 levels; and increases in C4 and interleukin-10 levels. These data suggest that daratumumab monotherapy warrants further exploration as a potential treatment for refractory LN.
Identification of human exTreg cells as CD16+CD56+ cytotoxic CD4+ T cells
Authors: Antoine Freuchet, Payel Roy, Sujit Silas Armstrong, Mohammad Oliaeimotlagh, Sunil Kumar, Marco Orecchioni, Amal J. Ali, Amir Khan, Jeffrey Makings, Qingkang Lyu, Holger Winkels, Erpei Wang, Christopher Durant, Yanal Ghosheh, Rishab Gulati, Felix Nettersheim, Klaus Ley
Journal: Nature Immunology (2023)
Metabolic rewiring induced by ranolazine improves melanoma responses to targeted therapy and immunotherapy
Authors: Marta Redondo-Muñoz, Francisco Javier Rodriguez-Baena, Paula Aldaz, Adriá Caballé-Mestres, Verónica Moncho-Amor, Maddalen Otaegi-Ugartemendia, Estefania Carrasco-Garcia, Ana Olias-Arjona, Irene Lasheras-Otero, Eva Santamaria, Ana Bocanegra, Luisa Chocarro, Abby Grier, Monika Dzieciatkowska M, Claudia Bigas, Josefina Martin, Uxue Urdiroz-Urricelqui, Florencio Marzo, Enrique Santamaria, Grazyna Kochan, David Escors, Ignacio Marcos Larrayoz, Holger Heyn, Angelo D’Alessandro, Camille Stephan-Otto Attolini, Ander Matheu, Claudia Wellbrock, Salvador Aznar Benitah, Berta Sanchez-Laorden, Imanol Arozarena
Journal: Nature Metabolism (2023)

Resistance of melanoma to targeted therapy and immunotherapy is linked to metabolic rewiring. Here, we show that increased fatty acid oxidation (FAO) during prolonged BRAF inhibitor (BRAFi) treatment contributes to acquired therapy resistance in mice. Targeting FAO using the US Food and Drug Administration-approved and European Medicines Agency-approved anti-anginal drug ranolazine (RANO) delays tumour recurrence with acquired BRAFi resistance. Single-cell RNA-sequencing analysis reveals that RANO diminishes the abundance of the therapy-resistant NGFRhi neural crest stem cell subpopulation. Moreover, by rewiring the methionine salvage pathway, RANO enhances melanoma immunogenicity through increased antigen presentation and interferon signalling. Combination of RANO with anti-PD-L1 antibodies strongly improves survival by increasing antitumour immune responses. Altogether, we show that RANO increases the efficacy of targeted melanoma therapy through its effects on FAO and the methionine salvage pathway. Importantly, our study suggests that RANO could sensitize BRAFi-resistant tumours to immunotherapy. Since RANO has very mild side-effects, it might constitute a therapeutic option to improve the two main strategies currently used to treat metastatic melanoma.
Insulin B peptide-MHC class II-specific chimeric antigen receptor-Tregs prevent autoimmune diabetes in mice
Authors: Justin A. Spanier, Vivian Fung, Christine M. Wardell, Mohannad H. Alkhatib, Yixin Chen, Linnea A. Swanson, Alexander J. Dwyer, Matthew E. Weno, Nubia Silva, Jason S. Mitchell, Paul C. Orban, Majid Mojibian, C. Bruce Verchere, Brian T. Fife, Megan K. Levings
Journal: Journal of Clinical Investigation (2023)

Adoptive immunotherapy with Tregs is a promising approach for prevention or treatment of type 1 diabetes. Islet antigen-specific Tregs have more potent therapeutic effects than polyclonal cells, but their low frequency is a barrier for clinical application. To generate Tregs that recognize islet antigens, we engineered a chimeric antigen receptor (CAR) derived from a monoclonal antibody with specificity for the insulin B-chain 10-23 peptide presented in the context of the IAg7 MHC class II allele present in NOD mice. Peptide specificity of the resulting InsB-g7 CAR was confirmed by tetramer staining and T cell proliferation in response to recombinant or islet-derived peptide. The InsB-g7 CAR re-directed NOD Treg specificity such that insulin B 10-23-peptide stimulation enhanced suppressive function, measured via reduction of proliferation and IL-2 production by BDC2.5 T cells and CD80 and CD86 expression on dendritic cells. Co-transfer of InsB-g7 CAR Tregs prevented adoptive transfer diabetes by BDC2.5 T cells in immunodeficient NOD mice. In wild type NOD mice, InsB-g7 CAR Tregs prevented spontaneous diabetes. These results show that engineering Treg specificity for islet antigens using a T cell receptor-like CAR is a promising new therapeutic approach for the prevention of autoimmune diabetes.
Pathogenic myelin-specific antibodies in multiple sclerosis target conformational proteolipid protein 1–anchored membrane domains
Authors: Gregory P. Owens, Timothy J. Fellin, Adeline Matschulat, Vanessa Salas, Kristin L. Schaller, Katherine S. Given, Alanna M. Ritchie, Andre Navarro, Kevin Blauth, Ethan G. Hughes, Wendy B. Macklin, Jeffrey L. Bennett
Journal: Journal of Clinical Investigation (2023)

B cell clonal expansion and cerebrospinal fluid (CSF) oligoclonal IgG bands are established features of the immune response in multiple sclerosis (MS). Clone-specific IgG1 monoclonal recombinant antibodies (rAbs) derived from MS patient CSF plasmablasts bound to conformational proteolipid protein 1 (PLP1) membrane complexes and, when injected into mouse brain with human complement, recapitulated histologic features of MS pathology: oligodendrocyte cell loss, complement deposition, and CD68+ phagocyte infiltration. Conformational PLP1 membrane epitopes were complex and governed by the local cholesterol and glycolipid microenvironment. Antibodies against conformational PLP1 membrane complexes targeted multiple surface epitopes, were enriched within the CSF compartment, and were detected in most MS patients but not in inflammatory and non-inflammatory neurologic controls. CSF PLP1 complex antibodies provide a pathogenic autoantibody biomarker specific for MS.
We need to focus on the health of women subject to pre-birth and infant care proceedings
Authors: Naomi Delap, Kirsty Kitchen
Journal: BMJ (2023)

Women subject to care proceedings during and after birth are being lost in the system; a national commitment is needed to improve support and health care for these women and their babies, write <b>Naomi Delap</b> and <b>Kirsty Kitchen</b>
Target delivery of a PD-1-TREM2 scFv by CAR-T cells enhances anti-tumor efficacy in colorectal cancer
Authors: Jian Chen, Tianchuan Zhu, Guanmin Jiang, Qi Zeng, Zhijian Li, Xi Huang
Journal: Molecular Cancer (2023)

Abstract Background Chimeric antigen receptor (CAR) -T cell therapy is an efficient therapeutic strategy for specific hematologic malignancies. However, positive outcomes of this novel therapy in treating solid tumors are curtailed by the immunosuppressive tumor microenvironment (TME), wherein signaling of the checkpoint programmed death-1 (PD-1)/PD-L1 directly inhibits T-cell responses. Although checkpoint-targeted immunotherapy succeeds in increasing the number of T cells produced to control tumor growth, the desired effect is mitigated by the action of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) in the TME. Previous studies have confirmed that targeting triggering-receptor-expressed on myeloid cells 2 (TREM2) on TAMs and MDSCs enhances the outcomes of anti-PD-1 immunotherapy. Methods We constructed carcinoembryonic antigen (CEA)-specific CAR-T cells for colorectal cancer (CRC)-specific antigens with an autocrine PD-1-TREM2 single-chain variable fragment (scFv) to target the PD-1/PD-L1 pathway, MDSCs and TAMs. Results We found that the PD-1-TREM2-targeting scFv inhibited the activation of the PD-1/PD-L1 pathway. In addition, these secreted scFvs blocked the binding of ligands to TREM2 receptors present on MDSCs and TAMs, reduced the proportion of MDSCs and TAMs, and enhanced T-cell effector function, thereby mitigating immune resistance in the TME. PD-1-TREM2 scFv-secreting CAR-T cells resulted in highly effective elimination of tumors compared to that achieved with PD-1 scFv-secreting CAR-T therapy in a subcutaneous CRC mouse model. Moreover, the PD-1-TREM2 scFv secreted by CAR-T cells remained localized within tumors and exhibited an extended half-life. Conclusions Together, these results indicate that PD-1-TREM2 scFv-secreting CAR-T cells have strong potential as an effective therapy for CRC.
Author Correction: CD40 signal rewires fatty acid and glutamine metabolism for stimulating macrophage anti-tumorigenic functions
Authors: Pu-Ste Liu, Yi-Ting Chen, Xiaoyun Li, Pei-Chun Hsueh, Sheue-Fen Tzeng, Hsi Chen, Pei-Zhu Shi, Xin Xie, Sweta Parik, Mélanie Planque, Sarah-Maria Fendt, Ping-Chih Ho
Journal: Nature Immunology (2023)
P926: ELEVATED SERUM LEVELS OF SOLUBLE B-CELL MATURATION ANTIGEN AS A PROGNOSTIC BIOMARKER FOR MULTIPLE MYELOMA
Authors: Juan Du, Pei Guo, Yun Wang, Haiyan He, Dongjian Chen, Jin Liu, Wanting Qiang, Jing Lu, Yang Liang
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Serum B-cell maturation antigen (sBCMA) levels can serve as a sensitive biomarker in multiple myeloma (MM). In the research setting, sBCMA levels can be accurately detected by enzyme-linked immunosorbent assay (ELISA), but the approach has not been approved for clinical us. Aims: The objective of this study is to use a novel chemiluminescence-based method to assess the clinical implication of sBCMA in the diagnosis, monitoring, and prognosis prediction of MM. Methods: We used a novel chemiluminescence method to assess sBCMA levels in 759 serum samples from 17 healthy donors and 443 patients with plasma cell (PC) diseases including AL amyloidosis, POEMS syndrome and MM. Results: Serum BCMA levels were elevated 16.1-fold in patients with newly diagnosed MM compared to healthy donors and rare PC diseases patients (P=0.0002). Specifically, the sBCMA levels in patients with progressive disease were 64.6-fold higher than those who showed partial response or above to treatment (P < 0.0001). The sBCMA level also correlated negatively with the response depth of MM patients. In newly diagnosed and relapsed MM patients, survival was significantly longer among those subjects whose sBCMA levels are below the median levels compared with those above the median value (P < 0.05). We optimized the accuracy of the survival prediction further by integrating sBCMA level into the Second Revised International Staging System (R2-ISS). Summary/Conclusion: Our findings provide evidence that the novel chemiluminescence method is sensitive and practical for measuring sBCMA levels in clinical samples and confirm that sBCMA might serve as an independent prognostic biomarker for MM. Keywords: Myeloma
PB2351: TRIAL IN PROGRESS: A PHASE 2, MULTICENTRE STUDY OF BRENTUXIMAB VEDOTIN WITH CHEMOTHERAPY IN FRONTLINE TREATMENT OF CHINESE PATIENTS WITH CD30-POSITIVE PERIPHERAL T-CELL LYMPHOMAS
Authors: Yuqin Song, Helen Wu, Meng Ji, Wenhan Jiang, Cassie Dong, Jun Zhu
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous, rare and aggressive group of mature T and NK cells neoplasms, representing 10% of newly diagnosed lymphoma in China. CD30 expression is a hallmark of diagnosis in systemic anaplastic large cell lymphoma (sALCL) and is well documented in some other most common PTCL subtypes. ECHELON-2 have shown significant improvement in progression-free survival (PFS) and overall survival (OS) with CD30-directed monoclonal antibody-drug conjugate, brentuximab vedotin (BV) in combination with cyclophosphamide, doxorubicin (hydroxydaunorubicin), prednisone (CHP) regimen in patients with treatment naïve CD30-positive PTCL, comparing with cyclophosphamide, doxorubicin (hydroxydaunorubicin), vincristine, prednisone (CHOP) regimen. In order to determine the efficacy and safety of BV combined with CHP regimen in Chinese population with untreated PTCL, a bridging study was planned to be conducted. Aims: To investigate the efficacy, safety, and PK of BV+CHP in the frontline treatment of Chinese patients with CD30+ PTCL. Methods: This phase 2, single-arm, open-label, multicenter study will include patients aged ≥18 years with newly diagnosed CD30+ PTCL and ECOG performance status ≤2. Following histological subtypes will be included - anaplastic lymphoma kinase (ALK)-positive sALCL with ≥2 International Prognostic Index score, ALK-negative sALCL, PTCL-not otherwise specified, angioimmunoblastic T-cell lymphoma, enteropathy-associated T-cell lymphoma, and hepatosplenic T-cell lymphoma. Patients will receive 1.8 mg/kg of BV intravenously for 30 mins on day 1 of 21-day cycle followed by IV administration of cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2) and daily oral dose of 100 mg of prednisone from day 1 to 5. The treatment will be continued until first occurrence of any one of these criteria: Progressive disease, unacceptable toxicity, or completion of the desired 6 to 8 cycles. The study will recruit approximately 52 patients including 36 patients with diagnosis of sALCL. Overall response rate (ORR) following the completion of study treatment as assessed by independent review facility and adverse events will be the primary endpoints. The secondary endpoints will include complete response rate following the completion of study treatment, 1-year PFS and OS rate, time to response (TTR), duration of response, pharmacokinetic analyses and antidrug antibody status. Results:Summary/Conclusion: The results from this bridging study will determine if they are consistent with results from global population and may provide support for the use of BV in treatment of Chinese patients with CD30+ PTCL. Study registration number: NCT05673785. Keywords: ALK/ALCL, CD30, Adult, Peripheral T-cell lymphoma
PB2482: ROXADUSTAT SUPPRESSES ADIPOGENESIS IN HUMAN BMMSC AND PROMOTES EPO PRODUCTION VIA REGULATION OF HIF SIGNALING PATHWAYS
Authors: Jing Zhang, Hui-Juan Ren, LI-Xia Cao, Lan Yang, Qiu-Yu Chen, Yan-Qiu Han#
Journal: HemaSphere (2023)

Topic: 23. Hematopoiesis, stem cells and microenvironment Background: Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, has been used to treat anemia in patients with chronic kidney diseases by increasing erythroprotein(EPO) levels. EPO is an important cytokine required for hematopoiesis which is also secreted by bone marrow niche. Roxadustat is reported closed with the HIF signaling pathways, which is also important for regulation of EPO production. However, there is few data about the effects of roxadustat on the bone marrow microenvironment. Aims: The aim of the study was to explore the effects of roxadustat on the adipogenesis in human bone marrow mesenchymal stem cell(hBMMSC) and the underlying molecular mechanisms. Methods: The Oil Red O staining was used to assess lipid accumulation of adipogenesis in hBMMSC. Western blot was used to determine the protein levels of potential signaling pathways. Elisa was used to test the EPO levels. Results: Roxadustat could obviously inhibit the adipogenic ability in hBMMSC cell line in a time- and dose-dependent manner, with downregulation of peroxisome proliferator-activated receptor γ(PPARγ) and CAAT/enhancer binding protein(C/EBP)-β. Additionally, we observed upregulation of HIF-1α and PHD3. Elisa results demonstrated that, with the suppression of adipogenesis, the level of EPO increased significantly. Summary/Conclusion: Roxadustat could suppress adipogenesis in hBMMSC and promote production of EPO, which might be via regulation of HIF-PHD signaling pathways. Roxadustat might be a potential agent for the hematopoiesis by interacting with MSC in the bone marrow microenvironment. Keywords: EPO, Mesenchymal stem cell
Decongestion strategies in patients presenting with acutely decompensated heart failure: A worldwide survey among physicians
Authors: Ali Vazir, Chris J. Kapelios, Elif Agaoglu, Marco Metra, Yury Lopatin, Petar Seferovic, Wilfred Mullens, Gerasimos Filippatos, Giuseppe Rosano, Andrew J.S. Coats, Ovidiu Chioncel
Journal: European Journal of Heart Failure (2023)
Diastolic exercise stress testing in heart failure with preserved ejection fraction: The <scp>DEST‐HF</scp> study
Authors: Simon Wernhart, Annika Goertz, Juergen Hedderich, Maria Papathanasiou, Julia Hoffmann, Tienush Rassaf, Peter Luedike
Journal: European Journal of Heart Failure (2023)

Pulmonary capillary wedge pressure (PAWP) ≥25 mmHg during bicycle ergometry is recommended to uncover occult heart failure with preserved ejection fraction. We hypothesized that PAWP increase would differ in available diastolic stress tests and that the margin of PAWP ≥25 mmHg would only be reliably achieved through ergometry.We conducted a prospective, single-arm study in patients with an intermediate risk for heart failure with preserved ejection fraction according to the ESC HFA-PEFF score. A total of 19 patients underwent four stress test modalities in randomized order: leg raise, fluid challenge, handgrip, and bicycle ergometry. The primary outcome was the difference (Δ) between resting and exercise PAWP in each modality. Secondary outcomes were differences (Δ) in mean pulmonary artery pressure (mPAP), cardiac output (CO), as well as the ratios between mPAP and PAWP to CO. Compared to resting values, passive leg raise (Δ7.7 ± 8.0 mmHg, p = 0.030), fluid challenge (Δ9.2 ± 6.4 mmHg, p = 0.003), dynamic handgrip (Δ9.6 ± 7.5 mmHg, p = 0.002), and bicycle ergometry (Δ22.3 ± 5.0 mmHg, p < 0.001) uncovered increased PAWP during exercise. Amongst these, bicycle ergometry also demonstrated the highest ΔmPAP (27.2 ± 7.1 mmHg, p < 0.001), ΔCO (3.3 ± 2.6 L/min, p < 0.001), ΔmPAP/CO ratio (2.3 ± 2.0 mmHg/L/min, p < 0.001), and ΔPAWP/CO ratio (2.2 ± 1.4 mmHg/L/min, p < 0.001) compared to other modalities. PAWP ≥25 mmHg was only reliably achieved in bicycle ergometry (31.1 ± 3.9 mmHg). In all other modalities only 10.5% of patients achieved PAWP ≥25 mmHg (handgrip 18.4 ± 6.6 mmHg, fluid 18.1 ± 5.6 mmHg, leg raise 16.5 ± 7.0 mmHg).We demonstrate that bicycle ergometry exhibits a distinct haemodynamic response with higher increase of PAWP compared to other modalities. This finding needs to be considered for valid detection of exercise PAWP ≥25 mmHg when non-bicycle tests remain inconclusive.